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1.
Environ Pollut ; 292(Pt B): 118482, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34763020

RESUMO

Living in walkable neighborhoods has been reported to be associated with a lower risk of cardiovascular disease. Features of walkable neighborhoods, however, may be related to particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5), which could increase risk of cardiovascular disease. The interaction effect between walkability and PM2.5 on risk of ischemic stroke remains to be elucidated. In this study, we recruited a total of 27,375 participants aged ≥40 years from Yinzhou District, Ningbo, Zhejiang Province, China to investigate the associations of walkability and PM2.5 with risk of ischemic stroke. We used amenity categories and decay functions to evaluate walkability and high-spatiotemporal-resolution land-use regression models to assess PM2.5 concentrations. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 4.08 years, we identified a total of 637 incident cases of ischemic stroke in the entire cohort. Higher walkability was associated with a lower risk of ischemic stroke (quartile, Q4 vs. Q1 walkability: HR = 0.59, 95% CI: 0.47-0.75), whereas PM2.5 was positively associated with risk of ischemic stroke (Q4 vs. Q1 PM2.5: HR = 1.70, 95% CI: 1.29-2.25). Furthermore, we observed a significant interaction between walkability and PM2.5 on risk of ischemic stroke. Walkability was inversely associated with risk of ischemic stroke at lower PM2.5 concentrations, but this association was attenuated with increasing PM2.5 concentrations. Although walkable neighborhoods appear to decrease the risk of ischemic stroke, benefits may be offset by adverse effects of PM2.5 exposure in the most polluted areas. These findings are meaningful for future neighborhood design, air pollution control, and stroke prevention.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/epidemiologia , China/epidemiologia , Estudos de Coortes , Humanos , Material Particulado/análise , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia
2.
J Affect Disord ; 296: 434-442, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606808

RESUMO

BACKGROUND: Preventive intervention can significantly reduce the human and economic costs of postpartum depression (PPD) compared with treatment post-diagnosis. However, identifying women with a high PPD risk and making a judgement as to the benefits of preventive intervention is a major challenge. METHODS: This is a retrospective study of parturients that underwent a cesarean delivery. Control group was used as development cohort and validation cohort to construct the risk prediction model of PPD and determine a risk threshold. Ketamine group and development cohort were used to verify the risk classification of parturients by evaluating whether the incidence of PPD decreased significantly after ketamine treatment in high-risk for PPD population. RESULTS: The AUC for the development cohort and validation cohort of the PPD prediction model were 0.751 (95%CI:0.700-0.802) and 0.748 (95%CI:0.680-0.816), respectively. A threshold of 19% PPD risk probability was determined, with a specificity and sensitivity in the validation cohort are 0.766 and 0.604, respectively. After matching the high-risk group and the low-risk group by propensity score, the results demonstrated that PPD incidence significantly reduced in the high-risk group following ketamine, versus non-ketamine, intervention (p < 0.01). In contrast, intervention in the low-risk group showed no significant difference in PPD outcomes (p > 0.01). LIMITATION: Randomized trials are needed to further verify the feasibility of the model and the thresholds proposed. CONCLUSION: This prediction model developed in this study shows utility in predicting PPD risk. Ketamine intervention significantly lowers PPD incidence in parturients with a risk classification threshold greater than 19%.

3.
Brain Behav ; : e2414, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34775693

RESUMO

Mild traumatic brain injury (mTBI) is usually caused by a bump, blow, or jolt to the head or penetrating head injury, and carries the risk of inducing cognitive disorders. However, identifying the biomarkers for the diagnosis of mTBI is challenging as evident abnormalities in brain anatomy are rarely found in patients with mTBI. In this study, we tested whether the alteration of functional network dynamics could be used as potential biomarkers to better diagnose mTBI. We propose a sparse dictionary learning framework to delineate spontaneous fluctuation of functional connectivity into the subject-specific time-varying evolution of a set of overlapping group-level sparse connectivity components (SCCs) based on the resting-state functional magnetic resonance imaging (fMRI) data from 31 mTBI patients in the early acute phase (<3 days postinjury) and 31 healthy controls (HCs). The identified SCCs were consistently distributed in the cohort of subjects without significant inter-group differences in connectivity patterns. Nevertheless, subject-specific temporal expression of these SCCs could be used to discriminate patients with mTBI from HCs with a classification accuracy of 74.2% (specificity 64.5% and sensitivity 83.9%) using leave-one-out cross-validation. Taken together, our findings indicate neuroimaging biomarkers for mTBI individual diagnosis based on the temporal expression of SCCs underlying time-resolved functional connectivity.

4.
Hum Immunol ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34785098

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patient's immunological status and found dramatic changes in the IGH within the patient's immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion, and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones 2-3 weeks after the onset of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34, and IGHV4-39 in COVID-19 patients were more abundant than those of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.

5.
Cereb Cortex ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34791082

RESUMO

Limited sample size hinders the application of deep learning in brain image analysis, and transfer learning is a possible solution. However, most pretrained models are 2D based and cannot be applied directly to 3D brain images. In this study, we propose a novel framework to apply 2D pretrained models to 3D brain images by projecting surface-based cortical morphometry into planar images using computational geometry mapping. Firstly, 3D cortical meshes are reconstructed from magnetic resonance imaging (MRI) using FreeSurfer and projected into 2D planar meshes with topological preservation based on area-preserving geometry mapping. Then, 2D deep models pretrained on ImageNet are adopted and fine-tuned for cortical image classification on morphometric shape metrics. We apply the framework to sex classification on the Human Connectome Project dataset and autism spectrum disorder (ASD) classification on the Autism Brain Imaging Data Exchange dataset. Moreover, a 2-stage transfer learning strategy is suggested to boost the ASD classification performance by using the sex classification as an intermediate task. Our framework brings significant improvement in sex classification and ASD classification with transfer learning. In summary, the proposed framework builds a bridge between 3D cortical data and 2D models, making 2D pretrained models available for brain image analysis in cognitive and psychiatric neuroscience.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1510-1516, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627432

RESUMO

OBJECTIVE: To explore the role of follicular helper T cell (Tfh)/ follicular regulatory T cell (Tfr) imbalance in B-cell lymphoma (BCL). METHODS: Sixteen BCL patients who were admitted to the Department of Hematology of The First People's Hospital of Yichang and 20 healthy people from December 2019 to November 2020 were enrolled and respectively divided into observation group and control group. The levels of Tfh and Tfr in peripheral blood were detected by flow cytometry. The changes of Tfh, Tfr, and Tfh/Tfr ratio were compared and the relationship between Tfh/Tfr ratio and efficacy, prognosis was analyzed. RESULTS: Compared with the healthy controls, Tfh and Tfh/Tfr ratio in peripheral blood of the BCL patients increased (P<0.05, P<0.01), while levels of Tfr was decreased (P<0.01). After chemotherapy, Tfh and Tfh/Tfr ratio in peripheral blood of the BCL patients decreased significantly than before chemotherapy (P<0.01), but Tfr was no significant difference. Multivariate analysis showed that Tfh and Tfh/Tfr ratio were positively correlated with international prognostic index (IPI) score and Ann Arbor stage (r=0.626, 0.564, 0.573, 0.608, respectively), while Tfr negatively (r=-0.504, -0.542, respectively). According to the average value of Tfh/Tfr ratio at initial diagnosis, BCL patients were divided into Tfh/Tfr high ratio group and low ratio group. It was found that the complete remission (CR) rate, overall response rate (ORR), and survival time in the high ratio group were significantly lower than the low ratio group (P<0.01). CONCLUSION: There is an imbalance of Tfh/Tfr ratio in peripheral blood of the BCL patients, and those with a high Tfh/Tfr ratio have lower CR, ORR and shorter survival time.


Assuntos
Linfoma de Células B , Linfócitos T Auxiliares-Indutores , Citometria de Fluxo , Humanos , Células T Auxiliares Foliculares , Linfócitos T Reguladores
8.
Biodivers Data J ; 9: e72451, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703357

RESUMO

Background: Cerapanorpa Gao, Ma & Hua, 2016, an endemic genus of Panorpidae in central China's mountain regions, currently comprises 21 described species. Recently, the short-horned scorpionfly C.brevicornis (Hua & Li, 2007) was confirmed to contain two valid species by phylogeographic and morphological data. Individuals from the highlands of the eastern Bashan Mountains were suggested as a good species, separated from the original short-horned C.brevicornis. New information: Cerapanorpaalpina sp. nov. was described from the alpine zone of the eastern Bashan Mountains in central China. The new species differs from its congeners by the following combination of characters: male bearing an extra-short anal horn on posterior margin of tergum VI; paramere elongate, extending beyond the median tooth of gonostylus and curved laterally at basal half; female medigynium slightly constricted medially without dorsal basal plate. The species number of Cerapanorpa is raised to 22.

9.
J Mater Chem B ; 9(41): 8594-8603, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34705008

RESUMO

Peptide dendrimers have a broad application in biomedical science due to their biocompatibility, diversity, and multifunctionality, but the precision synthesis of high-molecule weight peptide dendrimers remains challenging. We here report the facile and liquid-phase synthesis of molecular level precision and amino-acid built-in polylysine (PLL) dendrimers with molecular weights as high as ∼60 kDa. Three types of polyhedral oligosilsesquioxane (POSS)-cored PLL dendrimers with phenylalanine, tyrosine, or histidine as building blocks were synthesized. The precise structures of the dendrimers were confirmed by MALDI-TOF MS, GPC, and 1H NMR spectroscopy. The interior functionalized peptide dendrimers improved the encapsulation capability of SN38 and sustained the release profiles. Enhanced molecular interactions between the peptide dendrimers and drugs were explored by both NMR experiments and computer simulations. The peptide dendrimer/SN38 formulations showed potent antitumor activity against multiple cancer cell lines. We believe that this strategy can be applied to the synthesis of tailor-made functional peptide dendrimers for drug-specific delivery and other diverse biomedical applications.

10.
Biomed Mater ; 16(6)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34670204

RESUMO

Collagen and chitosan are two different kinds of natural biodegradable polymers commonly used in the regeneration of bone defects. Mesoporous bioactive glass (MBG) is a type of favorable bone filler which can effectively constitute an enlarged microenvironment to facilitate an exchange of important factors between the cells and scaffolds. Here we prepared a collagen-chitosan-MBG (C-C-MBG) scaffold which displayed significantly increased proliferation, differentiation and mineralization in bone mesenchymal stem cells (BMSCs). Additionally, we found that the scaffold can stimulate extra-cellular signal regulated kinase 1/2 (Erk1/2) activated Runx2 pathway, which is the predominant signaling pathway involved in osteoblast differentiation. Consistently, we observed that the scaffold can markedly enhance the expression ofType I collagen, Osteopontin(Opn), andRunx2, which are important osteoblastic marker genes implicated in the process of osteoblast differentiation. Therefore, we conclude that the composite scaffold can significantly promote the differentiation of BMSCs into osteoblasts by activating Erk1/2-Runx2 pathway. Our finding thereby implies that the C-C-MBG scaffold can possibly act as a potential biomaterial in the bone regeneration.

11.
Am J Transl Res ; 13(8): 8754-8765, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539992

RESUMO

BACKGROUND: Increasing evidence has suggested that high uric acid (HUA) is closely related to cardiovascular disease (CVD). Mitophagy abnormalities have been reported to participate in multiple pathogenic processes of CVD. However, the potential molecular mechanisms remain unclear. Herein, we investigated the effect of HUA-induced mitophagy and its potential molecular mechanism in cardiomyocytes. METHODS: We established a model of cardiomyocytes induced by HUA in vitro and in vivo. Mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production and adenosine triphosphate (ATP) content were measured. The mitophagy-related protein expression of LC3B-II, Parkin, Ca2+/calmodulin-dependent protein kinase II δ (CaMKIIδ) and P62 was measured by Western blot. Based on the colocalization of lysosomes and mitochondria, a confocal microscope was used to detect mitophagy. Additionally, we established a mitophagy inhibitor group (3-MA) and CaMKIIδ inhibitor group (KN-93) to verify the pathway. RESULTS: In the HUA stimulation model, ROS production was increased, and mitochondrial injury indexes (MMP and ATP contents) were decreased. Moreover, these indicators were reversed by 3-MA and KN-93. Under HUA stimulation, the expression of LC3B-II, Parkin, CaMKIIδ and P62 increased significantly. Furthermore, these protein levels were reduced by 3-MA and KN-93. CONCLUSION: HUA can promote cardiomyocyte mitophagy activation through the ROS/CaMKIIδ/parkin pathway axis. This study may provide a new target and theoretical basis for the prevention and treatment of HUA-related metabolic heart disease in the future.

12.
Blood Purif ; : 1-8, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34569495

RESUMO

BACKGROUND: The objective of this study was to study the influence of extracorporeal blood flow rate (BFR) on the accuracy of central venous pressure (CVP) measurement during continuous renal replacement therapy (CRRT). METHODS: Eligible patients were randomly divided into 3 groups based on the location of catheters used for their CRRT and CVP measurement. CVP levels measured at increased extracorporeal BFR (from 0 to 300 mL/min) in the normal and reverse positions of inlet and outlet lines connected to the CV catheter (CVC) in the course of the CRRT session were collected. RESULTS: CVP levels measured at different extracorporeal BFRs did not significantly differ between and among the 3 groups. Inversion of inlet and outlet lines connected to the catheters did not affect the accuracy of CVP measurement. BFR had a negative correlation with inflow/access pressure but a positive correlation with outflow/return pressure. Neither inflow pressure nor outflow pressure was correlated with CVP. CONCLUSIONS: Extracorporeal BFR has no influence on the accuracy of CVP measurement during CRRT with the net machine balance adjusted to zero regardless of the location of the catheter and the connection method between catheters and CRRT lines. Thus, CRRT does not need to be discontinued to obtain an accurate CVP measurement.

13.
Neuroscience ; 476: 60-71, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34506833

RESUMO

Among the hypomyelinating leukodystrophies, Pelizaeus-Merzbacher disease (PMD) is a representative disorder. The disease is caused by different types of PLP1 mutations, among which PLP1 duplication accounts for ∼70% of the mutations. Previous studies have shown that PLP1 duplications lead to PLP1 retention in the endoplasmic reticulum (ER); in parallel, recent studies have demonstrated that PLP1 duplication can also lead to mitochondrial dysfunction. As such, the respective roles and interactions of the ER and mitochondria in the pathogenesis of PLP1 duplication are not clear. In both PLP1 patients' and healthy fibroblasts, we measured mitochondrial respiration with a Seahorse XF Extracellular Analyzer and examined the interactions between the ER and mitochondria with super-resolution microscopy (spinning-disc pinhole-based structured illumination microscopy, SD-SIM). For the first time, we demonstrated that PLP1 duplication mutants had closer ER-mitochondrion interfaces mediated through structural and morphological changes in both the ER and mitochondria-associated membranes (MAMs). These changes in both the ER and mitochondria then led to mitochondrial dysfunction, as reported previously. This work highlights the roles of MAMs in bridging PLP1 expression in the ER and pathogenic dysfunction in mitochondria, providing novel insight into the pathogenicity of mitochondrial dysfunction resulting from PLP1 duplication. These findings suggest that interactions between the ER and mitochondria may underlie pathogenic mechanisms of hypomyelinating leukodystrophies diseases at the organelle level.

14.
Mol Ecol Resour ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34549890

RESUMO

Populus has a wide ecogeographical range spanning the Northern Hemisphere, and interspecific hybrids are common. Populus tomentosa Carr. is widely distributed and cultivated in the eastern region of Asia, where it plays multiple important roles in forestry, agriculture, conservation, and urban horticulture. Reference genomes are available for several Populus species, however, our goals were to produce a very high quality de novo chromosome-level genome assembly in P. tomentosa genome that could serve as a reference for evolutionary and ecological studies of hybrid speciation throughout the genus. Here, combining long-read sequencing and Hi-C scaffolding, we present a high-quality, haplotype-resolved genome assembly. The genome size was 740.2 Mb, with a contig N50 size of 5.47 Mb and a scaffold N50 size of 46.68 Mb, consisting of 38 chromosomes, as expected with the known diploid chromosome number (2n = 2x = 38). A total of 59,124 protein-coding genes were identified. Phylogenomic analyses revealed that P. tomentosa is comprised of two distinct subgenomes, which we deomonstrate is likely to have resulted from hybridization between Populus adenopoda as the female parent and Populus alba var. pyramidalis as the male parent, with an origin of approximately 3.93 Ma. Although highly colinear, significant structural variation was found between the two subgenomes. Our study provides a valuable resource for ecological genetics and forest biotechnology.

15.
Cancer ; 127(21): 4030-4039, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34368955

RESUMO

BACKGROUND: Cervical cancer is 1 of the most common cancers in females worldwide. Understanding the most recent global patterns and temporal trends of cervical cancer burden might be helpful for its prevention and control. METHODS: Data on cervical cancer (International Classification of Diseases, Tenth Revision, code C53) incidence and mortality in 2018 were extracted from the GLOBOCAN 2018 database and further analyzed for their correlations with the Human Development Index. Temporal trends were analyzed using the annual percent change with joinpoint analysis among 31 countries with highly qualified data from the Cancer Incidence in Five Continents Plus and World Health Organization mortality databases. Future trends for the next 15 years were predicted using an open-source age-period-cohort model. RESULTS: Cervical cancer incidence and mortality rates were both negatively correlated with the Human Development Index (r = -0.56 for incidence, r = -0.69 for mortality; P < .001) in cross-sectional analysis, and both remained stable in 12 countries or even decreased in 14 and 18 countries for incidence and mortality, respectively, during the most recent 10 data years. Similar findings were observed for the next 15 years. CONCLUSIONS: Cervical cancer burden was correlated with socioeconomic development. An overwhelming majority of countries had stable or decreasing trends in incidence and mortality rates, especially in those with effective cervical cancer screening programs and human papillomavirus vaccination. LAY SUMMARY: The authors investigated the most up-to-date data from official databases released by the International Agency for Research on Cancer and found that cervical cancer incidence and mortality were negatively correlated with socioeconomic development. Among the 31 countries analyzed, most (26 countries were analyzed for incidence, and 30 were analyzed for mortality) had stable or even decreasing temporal trends over the most recent 10 years, especially in those with effective cervical cancer screening programs. In addition, the predicted trends for the next 15 years were basically consistent with the observed trends among most of the analyzed countries (19 countries for incidence and 26 countries for mortality).

16.
Ophthalmology ; 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34339778

RESUMO

PURPOSE: To develop and validate a multimodal artificial intelligence algorithm, FusionNet, using the pattern deviation probability plots from visual field (VF) reports and circular peripapillary OCT scans to detect glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional study. SUBJECTS: Two thousand four hundred sixty-three pairs of VF and OCT images from 1083 patients. METHODS: FusionNet based on bimodal input of VF and OCT paired data was developed to detect GON. Visual field data were collected using the Humphrey Field Analyzer (HFA). OCT images were collected from 3 types of devices (DRI-OCT, Cirrus OCT, and Spectralis). Two thousand four hundred sixty-three pairs of VF and OCT images were divided into 4 datasets: 1567 for training (HFA and DRI-OCT), 441 for primary validation (HFA and DRI-OCT), 255 for the internal test (HFA and Cirrus OCT), and 200 for the external test set (HFA and Spectralis). GON was defined as retinal nerve fiber layer thinning with corresponding VF defects. MAIN OUTCOME MEASURES: Diagnostic performance of FusionNet compared with that of VFNet (with VF data as input) and OCTNet (with OCT data as input). RESULTS: FusionNet achieved an area under the receiver operating characteristic curve (AUC) of 0.950 (0.931-0.968) and outperformed VFNet (AUC, 0.868 [95% confidence interval (CI), 0.834-0.902]), OCTNet (AUC, 0.809 [95% CI, 0.768-0.850]), and 2 glaucomatologists (glaucomatologist 1: AUC, 0.882 [95% CI, 0.847-0.917]; glaucomatologist 2: AUC, 0.883 [95% CI, 0.849-0.918]) in the primary validation set. In the internal and external test sets, the performances of FusionNet were also superior to VFNet and OCTNet (FusionNet vs VFNet vs OCTNet: internal test set 0.917 vs 0.854 vs 0.811; external test set 0.873 vs 0.772 vs 0.785). No significant difference was found between the 2 glaucomatologists and FusionNet in the internal and external test sets, except for glaucomatologist 2 (AUC, 0.858 [95% CI, 0.805-0.912]) in the internal test set. CONCLUSIONS: FusionNet, developed using paired VF and OCT data, demonstrated superior performance to both VFNet and OCTNet in detecting GON, suggesting that multimodal machine learning models are valuable in detecting GON.

18.
Transgenic Res ; 30(5): 663-674, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34304368

RESUMO

Herein, we investigate the high incidence of umbilical hernia and tippy-toe standing and their underlying changes in gene expression and proliferation in myostatin knockout (MSTN-/-) pigs. Thirty-six male MSTN-/- pigs were generated by somatic cell nuclear transfer (SCNT). These pigs presented a considerably high incidence of tippy-toe standing and umbilical hernia (69.4% and 61.1%, respectively). The tendon to body weight ratio was significantly lower than wild-type pigs (0.202 ± 0.017 vs 0.250 ± 0.004, respectively). The crimp length of the MSTN-/- tendon was significantly longer than that of wild-type pigs. The expression of MSTN and the activin type IIB (ACVR2B) was detected in the tendon and linea alba of MSTN-/- pigs. MSTN treatment significantly increased the phosphorylation of Smad2/3 in both tendon and linea alba fibroblasts. Type I collagen (Col1A) and Scleraxis (Scx) expression levels in the tendon and linea alba of MSTN-/- pigs were significantly lower than those in wild-type in vivo, whereas and cyclin-dependent kinase inhibitor 1 (p21) expression levels were higher. Treatment of tendon and linea alba fibroblasts with recombinant MSTN increased Col1A and Scx and decreased p21 expression in vivo. Moreover, there was a significant increase in fibroblast proliferation after treatment. The results indicated that MSTN regulates collagen expression and proliferation in tendon and linea alba fibroblasts; thus, MSTN deficiency causes collagen-related pathological features in MSTN-/- pigs. Hence, MSTN could be used as a therapeutic target for treating UH and tendon abnormalities.

19.
Orphanet J Rare Dis ; 16(1): 319, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281576

RESUMO

BACKGROUND: LAMA2-related muscular dystrophy including LAMA2-related congenital muscular dystrophy (LAMA2-CMD) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23) is caused by LAMA2 pathogenic variants. We aimed to describe the natural history and establish genotype-phenotype correlations in a large cohort of Chinese patients with LAMA2-related muscular dystrophy. METHODS: Clinical and genetic data of LAMA2-related muscular dystrophy patients enrolled from ten research centers between January 2003 and March 2021 were collected and analyzed. RESULTS: One hundred and thirty patients (116 LAMA2-CMD and 14 LGMDR23) were included. LAMA2-CMD group had earlier onset than LGMDR23 group. Head control, independent sitting and ambulation were achieved in 76.3%, 92.6% and 18.4% of LAMA2-CMD patients at median ages of 6.0 months (range 2.0-36.0 months), 11.0 months (range 6.0-36.0 months), and 27.0 months (range 18.0-84.0 months), respectively. All LGMDR23 patients achieved independent ambulation at median age of 18.0 months (range 13.0-20.0 months). Motor regression in LAMA2-CMD mainly occurred concurrently with rapid progression of contractures during 6-9 years old. Twenty-four LAMA2-related muscular dystrophy patients died, mostly due to severe pneumonia. Seizures occurred in 35.7% of LGMDR23 and 9.5% of LAMA2-CMD patients. Forty-six novel and 97 known LAMA2 disease-causing variants were identified. The top three high-frequency disease-causing variants in Han Chinese patients were c.7147C > T (p.R2383*), exon 4 deletion, and c.5156_5159del (p.K1719Rfs*5). In LAMA2-CMD, splicing variants tended to be associated with a relatively mild phenotype. Nonsense variants were more frequent in LAMA2-CMD (56.9%, 66/116) than in LGMDR23 (21.4%, 3/14), while missense disease-causing variants were more frequent in LGMDR23 (71.4%, 10/14) than in LAMA2-CMD (12.9%, 15/116). Copy number variations were identified in 26.4% of survivors and 50.0% of nonsurvivors, suggesting that copy number variations were associated with lower rate of survival (p = 0.029). CONCLUSIONS: This study provides better understandings of natural history and genotype-phenotype correlations in LAMA2-related muscular dystrophy, and supports therapeutic targets for future researches.


Assuntos
Distrofia Muscular do Cíngulo dos Membros , Distrofias Musculares , Criança , Pré-Escolar , China , Variações do Número de Cópias de DNA , Humanos , Lactente , Laminina/genética , Distrofias Musculares/genética
20.
Environ Int ; 156: 106726, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34175778

RESUMO

Exposure to ambient PM2.5 (fine particulate matter) can cause adverse effects on human health. China has been experiencing dramatic changes in air pollution over the past two decades. Statistically deriving ground-level PM2.5 from satellite aerosol optical depth (AOD) has been an emerging attempt to provide such PM2.5 data for environmental monitoring and PM2.5-related epidemiologic study. However, current countrywide datasets in China have generally lower accuracies with lower spatiotemporal resolutions because surface PM2.5 level was rarely recorded in historical years (i.e., preceding 2013). This study aimed to reconstruct daily ambient PM2.5 concentrations from 2000 to 2018 over China at a fine scale of 1 km using advanced satellite datasets and ground measurements. Taking advantage of the newly released Multi-Angle Implementation of Atmospheric Correction (MAIAC) 1-km AOD dataset, we developed a novel statistical strategy by establishing an advanced spatiotemporal model relying on adaptive model structures with linear and non-linear predictors. The estimates in historical years were validated against surface observations using a strict leave-one-year-out cross-validation (CV) technique. The overall daily leave-one-year-out CV R2 and root-mean-square-deviation values were 0.59 and 27.18 µg/m3, respectively. The resultant monthly (R2 = 0.74) and yearly (0.77) mean predictions were highly consistent with surface measurements. The national PM2.5 levels experienced a rapid increase in 2001-2007 and significantly declined between 2013 and 2018. Most of the discernable decreasing trends occurred in eastern and southern areas, while air quality in western China changed slightly in the recent two decades. Our model can deliver reliable historical PM2.5 estimates in China at a finer spatiotemporal resolution than previous approaches, which could advance epidemiologic studies on the health impacts of both short- and long-term exposure to PM2.5 at both a large and a fine scale in China.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Monitoramento Ambiental , Humanos , Material Particulado/análise
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